Candesartan prevents the progression of glomerulosclerosis in genetic hypertensive rats.

摘要: The renin-angiotensin system (RAS) has been implicated in the development of hypertensive glomerulosclerosis. However, there are no experimental findings clearly demonstrating activation glomerular RAS nephropathy. Using stroke-prone spontaneously rat (SHRSP) as an animal model glomerulosclerosis, we examined relationship between sequential changes urinary albumin excretion (UAE), renal morphology, and mRNA expression for transforming growth factor-beta (TGF-beta) fibronectin (FN) levels components, determined effects angiotensin II (Ang II) type 1 (AT-1) receptor antagonist (candesartan) equihypotensive hydralazine on these parameters. In SHRSP, UAE was normal at nine weeks age increased by 12 weeks. Plasma renin activity, plasma Ang concentration, converting enzyme (ACE) activity were not higher 9- 12-week-old SHRSP than WKY. RNase protection assay revealed angiotensinogen, ACE, AT-1a AT-1b receptors 9-, 12-, 14-week-old TGF-beta FN from age. had a greater glomerulosclerosis index (GSI) 24 did Administration candesartan two weeks, but hydralazine, markedly reduced normalized TGF-beta, FN, components. Candesartan administration virtually prevented progression rats. We conclude that sensitivity to glomeruli play important roles